Grades Of Non-alcoholic Fatty Liver Disease Research Articles

Is Helicobacter pylori infection a risk factor for non-alcoholic fatty liver disease in children?

Helicobacter pylori infection has been investigated as a potential risk factor for non-alcoholic fatty liver disease (NAFLD). Some studies suggest a possible link between the two conditions. The purpose of this study is to study the relationship between H. pylori infection and NAFLD in pediatrics and its relation to NAFLD grades. A case–control study to identify predictors of NAFLD and a comparative cross-sectional approach to determine factors affecting NAFLD grades were adopted. One hundred NAFLD children (ultrasound-based) and a control group of 100 non-NAFLD children were recruited. Both groups were evaluated by detecting H. pylori stool antigen. Immunoglobulin G antibodies to Cag A (cytotoxin-associated gene A), Vac A (vacuolating cytotoxin A), Gro EL (chaperonin Gro EL), HCPC (Helicobacter cysteine-rich protein C), and Ure A (Urease subunit A) were assessed in the serum of those with positive stool antigen. H. pylori infection was significantly higher in NAFLD children compared to the control group (64% versus 25%, p-value < .001). (NAFLD children showed higher Cag A and Vac A positivity (34, 10%) versus (2%, 0%) in the control group, respectively, p-value < .001). The regression model showed that H. pylori positivity (OR (odds ratio) = 5.021, 95% CI (confidence interval): 1.105–22.815), homeostatic model assessment of insulin resistance (Homa IR) (OR = 18.840, 95% CI: 3.998–88.789), waist percentile (OR = 1.184, 95% CI: 1.044–1.344), and triglycerides (OR = 1.029, 95% CI: 1.012–1.047) were predictors for NAFLD. Cag A positivity (OR = 2.740, 95% CI: 1.013–7.411) was associated with higher NAFLD grade (grade 2 fatty liver).Conclusions:H. pylori infection could increase the risk of NAFLD in children. Triglycerides, waist circumference, and Homa IR are significant independent predictors of NAFLD.What is Known:• NAFLD has become one of the most common liver diseases among children because of the increased prevalence of pediatric obesity.• Dyslipidemia and insulin resistance play a central role in NAFLD pathogenesis. • NAFLD could be explained by the multiple-hit hypothesis. The gut microbiota is an important factor in this hypothesis (gut liver axis).What is New:• Helicobacter pylori infection could increase the risk of NAFLD in children. • H. pylori Cytotoxin-associated gene A (Cag A) positivity is associated with higher NAFLD grade.

Impact of Nonalcoholic Fatty Liver Disease on Weight Loss Outcomes After One Anastomosis Gastric Bypass.

Obesity-associated nonalcoholic fatty liver disease (NAFLD) is a significant cause of chronic liver disease. Our study sought to investigate preoperative NAFLD and the effect at 6 months and 2 years after surgery of one anastomosis gastric bypass (OAGB) and its development 6 months after surgery regarding weight loss outcomes. A retrospective cohort study was conducted on patients with severe obesity who underwent primary OAGB at Hazrat-e-Rasool Hospital between March 2020 and June 2021. Preoperative assessments included abdominal ultrasound (US) for NAFLD grading, weight, and biochemical blood tests. Follow-up examinations were performed at 10 days and 1, 3, 6, 9, 12, and 24 months postsurgery, with subsequent US examinations at the 6-month follow-up. Two hundred thirty-one patients were included, with an average age of 40.3±10.5 years and a percentage of 78.4 women. Their mean weight and BMI were 131.2±26.8 and 48.8±8.5, respectively. Six-month grades of NAFLD showed that patients with grade 3 NAFLD had significantly lower TWL% compared with the lower grades. NAFLD grades improved in 72.3% of our patients, remained the same at 21.2%, and worsened at 6.5%. The 6-month TWL% was 28.4±4.3 in the no-change group, 28.4±5.3 for the improved group, and 25.2±14.6 in the worse group. The severity and progression of NAFLD can significantly impact weight loss outcomes post-OAGB, highlighting the importance of monitoring and managing NAFLD in patients undergoing bariatric surgery.

Fatty Liver Disease and its Impaction on Insulin Resistance

Abstract Background Non-alcoholic fatty liver disease (NAFLD) involves excess liver fat accumulation without specific causes like alcohol or viral infections, categorized into simple steatosis and nonalcoholic steatohepatitis (NASH). While simple steatosis is generally stable, NASH is linked to progressive liver disease. Diagnosis excludes secondary causes, and NAFLD, marked by hepatocyte changes, inflammation, and fibrosis, may lead to severe complications. Strongly associated with insulin resistance in liver and adipose tissues, NAFLD disrupts glucose-insulin interplay, compromising insulin's regulatory functions and contributing to metabolic disorders and disease progression. Aim of the Work The aim of the study is to investigate fatty liver disease and evaluate its impact of on insulin resistance. Patients and Methods This cross-sectional study, conducted at Ain Shams University, focuses on adults with NAFLD to assess insulin resistance. Inclusion criteria involve fatty liver disease, impaired glucose tolerance, and informed consent, while exclusions include alcohol intake and hepatitis. Data collection comprises demographics, anthropometrics, metabolic syndrome assessment, ultrasound grading of steatosis, and laboratory tests for liver function, FIB-4 index, and insulin resistance using HOMA-IR. The study aims to understand the relationship between NAFLD and insulin resistance in a clinical setting. Results In this study of 98 patients with Non-alcoholic Fatty Liver Disease (NAFLD), characterized by liver fat accumulation, insulin resistance (IR) was prevalent in 63.3%. The cases, predominantly females (52%), had mean age of 43 years, 50% were hypertensive, and 48% were diabetic. IR was directly related to age, and its prevalence was significantly higher in patients with diabetes and hypertension. IR correlated positively with body weight, BMI, ALT, AST, FIB-4, TG, and cholesterol. Fatty liver grading showed a significant association with IR, particularly in grade 2 cases. The optimal HOMA-IR cutoff for distinguishing between grade I and II fatty liver was &amp;gt;2.56, with high sensitivity (100%) and specificity (88.73%). These findings emphasize the intricate relationship between NAFLD, IR, and associated metabolic factors. Conclusion The study established a robust link between insulin resistance (IR) and Non- alcoholic Fatty Liver Disease (NAFLD), noting a 63.3% prevalence of IR in the subjects. Employing HOMA-IR, a cutoff point &amp;gt;2.56 effectively differentiated between NAFLD grades I and II, demonstrating 100% sensitivity, 88.73% specificity, and a remarkable AUC of 98. This underscores HOMA-IR's valuable role in identifying and stratifying NAFLD, especially in individuals with diabetes.

Association of nonalcoholic fatty liver disease with new-onset atrial fibrillation stratified by age groups

BackgroundThe association between nonalcoholic fatty liver disease (NAFLD) and atrial fibrillation (AF) has been inconsistent, and the impact of hepatic fibrosis on this relationship remains uncertain. We investigated the association between NAFLD and the risk of new-onset AF across different age groups.MethodsA total of 3,179,582 participants from the 2009 Korean National Health Screening Program were divided into five groups based on NAFLD status: no NAFLD (fatty liver index [FLI] < 30); grade 1 NAFLD without advanced fibrosis (FLI 30–59 & BARD < 2); grade 1 NAFLD with advanced fibrosis (FLI 30–59 & BARD ≥ 2); grade 2 NAFLD without advanced fibrosis (FLI ≥ 60 & BARD < 2); and grade 2 NAFLD with advanced fibrosis (FLI ≥ 60 & BARD ≥ 2). The primary outcome was incident AF.ResultsDuring the median follow-up of 9.3 years, 62,542 patients were diagnosed with new-onset AF. In the age- and sex-adjusted model, the risk of new-onset AF increased across NAFLD grades and fibrosis categories: grade 1 NAFLD without advanced fibrosis (hazard ratio [HR] 1.120, 95% confidence interval [CI]: 1.081–1.161); grade 1 NAFLD with advanced fibrosis (HR 1.275, 95% CI 1.251–1.300); grade 2 NAFLD without advanced fibrosis (HR 1.305, 95% CI: 1.252–1.360); and grade 2 NAFLD with advanced fibrosis (HR 1.627, 95% CI: 1.586–1.670). In the multivariate model, the excess risk of AF in patients with NAFLD and advanced fibrosis remained significant, even in participants aged 20–39 years.ConclusionPatients with NAFLD had a higher risk of new-onset AF, which increased progressively with NAFLD severity, particularly in those aged 20–29 years.

Serum Resistin Levels in Patients with Nonalcoholic Fatty Liver Disease in an Iranian Population

Introduction: Non-alcoholic fatty liver disease (NAFLD) is a major global health problem, in which liver fat exceeds 5% of the liver weight, without secondary causes of fat accumulation or excessive alcohol consumption. Resistin plays a key role in energy homeostasis, insulin resistance, inflammation, and metabolic disorders. This study aimed to investigate the relationship between resistin (RETN) level and NAFLD. Methods: In this cross-sectional study, 80 patients with NAFLD and 80 healthy individuals as controls were evaluated. Biochemical variables, liver enzymes, insulin, and resistin were measured. Data were analyzed using SPSS version 16 software. Results: The variables of cholesterol, insulin, triglyceride, HDL, body mass index, age, and liver enzymes were significantly different between the two groups of patients with NAFLD and healthy individuals (p&lt;0.05). In patients, resistin was associated with triglyceride (r=0.243, p=0.045). No association was found between resistin level and NAFLD grades (p≥0.05). Conclusion: The results of this study indicate that there is a relationship between resistin and NAFLD. There is no association between resistin level and the degree of NAFLD.

Recent Progresses on Pathophysiology, Diagnosis, Therapeutic Modalities, and Management of Non-alcoholic Fatty Liver Disorder

Abstract: Non-alcoholic fatty liver disease (NAFLD) is currently the utmost common chronic liver disorder that happens through all age groups and is identified to occur in 14%-30% of the general population, demonstrating a critical and grossing clinical issue because of the growing incidence of obesity and overweight. From the histological aspect, it looks like alcoholic liver damage, but it happens in patients who avoid remarkable alcohol usage. NAFLD comprises a broad spectrum, ranging from benign hepatocellular steatosis to inflammatory nonalcoholic steatohepatitis (NASH), different levels of fibrosis, and cirrhosis. Patients with NASH are more susceptible to more rapid progression to cirrhosis and hepatocellular carcinoma. There is no single factor that drives proceeding from simple steatosis to NASH. However, a combination of multi parameters such as genetic background, gut microflora, intake of high fat/ fructose dietary contents or methionine/choline-deficient diet, and consequently accumulated hepatocellular lipids mainly including triglycerides and also other bio-analytes, such as free fatty acids, cholesterol, and phospholipids display a crucial role in disease promotion. NAFLD is related to overweight and insulin resistance (IR) and is regarded as the hepatic presentation of the metabolic syndrome, an amalgamation of medical statuses such as hyperlipidemia, hypertension, type 2 diabetes, and visceral obesity. Despite the increasing prevalence of this disease, which imposes a remarkable clinical burden, most affected patients remain undiagnosed in a timely manner, largely related to the asymptomatic entity of NAFLD patients and the unavailability of accurate and efficient noninvasive diagnostic tests. However, liver biopsy is considered a gold standard for NAFLD diagnosis, but due to being expensive and invasiveness is inappropriate for periodic disease screening. Some noninvasive monitoring approaches have been established recently for NAFLD assessment. In addition to the problem of correct disease course prediction, no effective therapeutic modalities are approved for disease treatment. Imaging techniques can commonly validate the screening and discrimination of NAFLD; nevertheless, staging the disease needs a liver biopsy. The present therapeutic approaches depend on weight loss, sports activities, and dietary modifications, although different insulin-sensitizing drugs, antioxidants, and therapeutic agents seem hopeful. This review aims to focus on the current knowledge concerning epidemiology, pathogenesis, and different biochemical experiments and imaging modalities applied to diagnose the different grades of NAFLD and its management, as well as new data about pharmacological therapies for this disorder.

Histopathological Association of Non-alcoholic Fatty Liver Disease With Coronary Artery Atherosclerosis Grade

Background: The association between the severity of coronary atherosclerosis and histopathologic findings in patients with non-alcoholic fatty liver disease (NAFLD) is not entirely understood. Considering the gold standard method, this study evaluates the histopathologic association between the severity of NAFLD and the grades of coronary atherosclerosis. Methods: In this descriptive-analytical study, data from 205 cadavers who were referred to an Iranian (Tabriz) forensic medicine organization between 2015 and 2017 and underwent simultaneous liver and coronary artery biopsies were examined. Finally, 168 cases were entered based on the inclusion criteria. First, pathological slides of these cadavers were extracted from the forensic medicine archive and re-examined. Then, the selected cases’ blocks were extracted from the tissue block bank, and again, after preparing a new slide, they were stained with trichrome for accurate estimation of liver fibrosis. Results: The assessment of NAFLD histological status in the studied cases revealed that 75.6% of the cases were classified as severity I, 18.4% as severity II, and 6% as severity III. Most cases with coronary atherosclerosis were classified as American Heart Association staging (AHA), type V (19.6%), and normal (19.6%). There was no statistically significant relationship between the severity of simple steatosis, steatohepatitis, and NAFLD, with coronary atherosclerosis. In subjects with higher severity of coronary atherosclerosis, the liver fibrosis rate is also higher, but no statistically significant difference was observed. Conclusion: The present study revealed no significant histopathological association between NAFLD and coronary artery atherosclerosis grade.

Cardiovascular Disease (CVD) risk factors among patients of type2 Diabetes Mellitus (DM) with Non–Alcoholic Fatty Liver Disease (NAFLD)

Background: Global pandemics of cardiovascular disease (CVD) and diabetes mellitus (DM) are spreading quickly. CVD continues to be a pressing global health issue, standing as a prominent cause of both mortality and morbidity. Among its diverse risk factors, type2 DM and Non–Alcoholic Fatty Liver Disease (NAFLD) stand out as pivotal contributors. This research endeavors to delve into the multifaceted relationship between type2 DM, NAFLD, and cardiovascular health. Material &amp; Methods: From July 1 to December 31, 2012, a hospital-based observational study was conducted in the Department of Medicine at Cumilla Medical College and Hospital in Bangladesh. This study comprised 50 type2 DM patients with NAFLD who had been hospitalized. Their medical history, physical exam, and laboratory study (fasting and 2-hour post-meal blood glucose, blood urea, serum creatinine, liver function tests, and fasting lipid profile) were included. Based on a liver ultrasound examination, NAFLD was identified. Results: Out of 50 patients, 18(36%) were males and 32(64%) were females, with mean age 58.89 ± 8.38 and 54.6 ± 10.1 years, respectively. Grade -1 NAFLD cases were 54%, grade -2 was 32%, and grade -3 was 14%. On statistical analysis, we found increasing grades of NAFLD were significantly associated with hypertension (p=0.0083), obesity (p=0.0006), increasing levels of total cholesterol (p&lt;0.0001), ALT (p&lt;0.0001), AST (p&lt;0.0001) and ALP (p&lt;0.0001). Conclusions: NAFLD combines with CVD risk factors among people with type2 diabetes. It is a substitute and a reliable CVD risk marker in type2 diabetes patients. Ultrasonography was used to detect NAFLD.

Prospective Study to Analyze the Concordance Between a Standardized Visual Method With Pathology to stratify Nonalcoholic Fatty Liver Disease in Cadaveric Liver Grafts Evaluated for Transplantation.

The main challenge of liver transplantation is the discrepancy in demand and availability. Marginal grafts or full organs from donors with expansion criteria have been considered to reduce the shortage and assist a greater number of patients. Nonalcoholic fatty liver disease (NAFLD) is one of the most important defining criteria for expanded criteria organs. The present study proposes that an organized visual analysis method could correctly identify and classify NAFLD and organ viability without the need for liver biopsy and its logistical concerns. Pictures from the grafts were taken at a standardized method (same distance, light conditions, and register device) before and after the perfusion. The visual liver score (VLS) was applied by transplant surgeons; biopsies of the grafts were analyzed by a pathologist in a double-blind design. Score performance and interobserver agreement for NAFLD detection and grading, as graft viability evaluation, were calculated. Fifty-seven grafts were analyzed. At least 1 previous expansion criterion was presented by 59.64% of donors. The prevalence of NAFLD was 94.73%, with 31.57% borderline nonalcoholic steatohepatitis and 5.26% nonalcoholic steatohepatitis. Steatosis was identified with 48.68% (preperfusion) and 64.03% (postperfusion) accuracy. NAFLD stratification was performed with 49.53% (preperfusion) and 46.29% (postperfusion) accuracy. Viability related to NAFLD was identified with 51.96% (preperfusion) and 48.52% (postperfusion) accuracy. Interobserver agreement was moderate for total VLS and poor for individual components of VLS. Although a standardized method was not reliable enough for visual evaluation of NALFD compared with pathology, efforts should be made to expand access to biopsy. Further studies are needed to understand whether the VLS needs to be adapted or even excluded in the liver transplant scenario, to assess the importance of ectoscopy related to posttransplant clinical outcomes, and to determine its role in graft selection.

Weight loss induced alleviation of sleep-disordered breathing is associated with improvement of non-alcoholic fatty liver disease

IntroductionSleep-disordered breathing (SDB) and non-alcoholic fatty liver disease (NAFLD) are both common comorbidities in obese patients. Structured weight loss programs are effective and can reduce the incidence and severity of obesity-related comorbidities. The objective of the present analysis is to test whether weight loss induced alleviation of SDB is a predictor for improvement of NAFLD. MethodsObese participants underwent a standardized non-surgical 3 months weight reduction program (800 kilocalories per day with low carbohydrate and fat content). Abdominal sonography for NAFLD (grade 0 to 3) and monitoring for SDB (defined as apnea-hypopnea index [AHI] ≥ 15/h) were performed at baseline and after 3 months. Alleviation of SDB was defined as a shift from AHI≥ 15/h to <15/h. Results48 patients (48% female, age 42 ± 12 years, body-mass index 40.3 ± 8.1 kg/m2, AHI 14 ± 17/h, 85% NAFLD grade ≥1) participated in the weight loss program. In contrast to the no SDB group, in patients with SDB weight loss of 27.1 ±0 .9 kg (8.4 ± 2.8 kg/m2) after three months was paralleled by a reduction in AHI (-22 ± 17/h), prevalence of SDB (from 31% to 13%), and oxidized low-density lipoprotein (-13 ± 11 U/l). In individuals with preexisting SDB NAFLD grade improved more (2 versus 1, p<0.001) and was at a lower degree at 3 months than in those without SDB (0 versus 1, p = 0.015). In multivariable analysis models, SDB at baseline was associated with improvement of NAFLD grade (B 0.908; 95% CI 0.125, 1.691; p = 0.024), independently of age, sex, and BMI (each p>0.05, respectively). Decreasing BMI (B 0.16 [95%-CI 0.08; 0.23], p<0.001) and alleviation of SDB (B 0.90 [95%-CI 0.21; 1.58], p = 0.012) were independently associated with improvement of NAFLD grade. ConclusionPreexisting SDB and weight loss induced alleviation of SDB are predictors for improvement in NAFLD grade, independent of the extent of weight loss. SDB may contribute to the pathogenesis of NAFLD via SDB-induced oxidative stress and inflammation, but the causal mechanism remains unclear.

High Risk NAFLD among Patients with Irritable Bowel Syndrome: Frequency &amp; Effect on Disease Severity

Abstract Background Irritable bowel syndrome (IBS) is a functional gastrointestinal (GI) disease that significantly affects patient quality of life, interfere with daily activities, physical intimacy, traveling, and self-esteem. Because of its clinical heterogeneity and the unclear etiology of IBS, robust biomarkers and therapeutic targets for IBS are difficult to identify. On the other side, Non-alcoholic fatty liver disease (NAFLD) has become a common disease worldwide, affecting 25% of the adult population. Aim of the Work The aim of the study is to detect if there is a prevalent relation between those two diseases and the assessment of NAFLD prevalence and severity in IBS patients. Patients and Methods Our study has involved 75 patients with different degrees of IBS syndrome and variable severity patterns of NAFLD. Using inclusion and exclusion criteria for selecting the patients; IBS diagnosed according to modified ROME IV critera regardless of the type either constipation predominance or diarrhea predominance. While NAFLD was mainly detected using abdominal ultrasonography, both were differentiated into three grades determining the severity of each and their correlation. Results Our current study included 75 patients diagnosed with IBS (37 males and 38 females). Mean age of included patients was 42.17 ± 8.3 years. Mean height of included patients was 173.6 ± 9.07 cm, mean weight was 88.02 ± 14.9 Kg while mean BMI was 29.39 ± 4.4. Regarding evaluating the association of IBS with NAFLD there were high statisitical significant assocaiton between both diseases. The study of lipid profile parameters and liver enzymes in relation to IBS grade revealed no-significant association. The study of IBS grade regarding liver enzymes revealed no significant statistical difference between grades of IBS. Study of lipid profile parameters (S.cholesterol, S.triglycerides and LDL) in relation to U/S grade revealed high significant association between increased serum TAG and severe grade of NAFLD. Conclusion IBS had higher frequency of NAFLD. Also, there is significant association between IBS and NAFLD severity.

Sonological grading of non-alcoholic fatty liver and comparison with liver enzymes

Background: Non-alcoholic fatty liver disease (NAFLD) is becoming more well acknowledged as a significant contributor to liver-related morbidity and mortality. Objectives: To assess the sonological grading of non-alcoholic fatty liver disease and comparison with liver enzymes. Methods: An analytical cross-sectional study was conducted from 2022 August to 2023 January among the patients referred to radiology unit for liver sonography with diagnosis of non-alcoholic liver disease. Ethical approval was obtained from the institutional review committee of Kathmandu Medical College (Ref. 12082022/06). A convenience sampling method was used. The sample size calculated was 107. Descriptive statistics (frequencies, means, and standard deviations) was used to describe the variables of interest. One-way analysis of variance was applied for comparison of serum liver enzymes in between various grades of NAFLD at 5% significance level. Results: Mean age of the patients was 37.9 ± 17.8 years, with 60% females. Most patients had grade I NAFLD (82, 76.6%), whereas 23 (21.5%) were of grade II. Levels of liver enzyme: Serum glutamic pyruvic transaminase (SGPT) with p-value 0.02 and serum glutamic oxaloacetic transaminase (SGOT) with p-value 0.03 were associated with fatty liver grade. Conclusion: Ultrasound-based grading of the severity of NAFLD was associated with abnormalities in the liver enzyme profile of patients. The SGPT and SGOT levels correlated with increasing severity of NAFLD based on ultrasound.

Diagnostic Performance of Greyscale Ultrasound in Detecting Fatty Liver Disease in a Type 2 Diabetes Population Using FibroScan as the Reference Standard.

Introduction Brightness mode ultrasound (B-mode US) and FibroScan (Echosens, Paris, France) are the two ultrasound methods often recommended for screening non-alcoholic fatty liver disease (NAFLD) in persons with type 2 diabetes mellitus (T2DM). This study assessed the diagnostic performance of B-mode US using FibroScan as the reference standard. Methods Persons with a known history of T2DM were invited to screen for NAFLD using B-mode US and FibroScan on separate days within a one-month period. Assessors of B-mode US and FibroScan were blinded to each other's findings. Both B-mode US and FibroScan independently assessed and graded each participant for the presence of NAFLD. Using the diagnostic test findings of FibroScan as a reference standard, the sensitivity and specificity of B-mode US were analyzed.The area under the receiver operating characteristic curve (AUROC) was analyzed using Jamovi (version 2.3.21). A multinomial logistic regression of the B-mode US and FibroScan in predicting NAFLD grade was also analyzed. Results A total of 171 participants were assessed. B-mode US detected NAFLD in T2DM patients with 63.6% sensitivity, 65.6% specificity, and 0.646 AUROC. Sensitivity and specificity in overweight and obese participants were 36-43% and 76-85%, respectively. Multinomial logistic regression demonstrated an insignificant statistical relationship between FibroScan and B-mode US in predicting grade 1 steatosis (p-value = 0.397), which was significantly affected by a higher BMI (p-value = 0.034) rather than a higher liver fibrosis level (p-value = 0.941). The logistic regression further showed a significant relationship between B-mode US and FibroScan in predicting steatosis grade 2 (p-value = 0.045) and grade 3 (p-value < 0.001), which was not significantly affected by BMI (p-value = 0.091). Conclusion B-mode US can replace FibroScan for severe steatosis; however, it cannot be used to screen for NAFLD in T2DM patients due to lower sensitivity for early detection in the overweight.

Evaluation of the effectiveness of long-term complex treatment schemes for patients with non-alcoholic fatty liver disease in combination with renal parenchymal arterial hypertension

Objective — to evaluate the effectiveness and safety of the use of original schemes of complex treatment of patients with non‑alcoholic fatty liver disease (NAFLD) and renal parenchymal arterial hypertension (RPAH).&#x0D; Materials and methods. Investigation involved 45 patients with NAFLD and RPAH grade 2. The state of the liver was assessed with ultrasound examination. Liver steatosis, inflammation and fibrosis were evaluated with the use of FibroMax test (France). Blood biochemistry was analyzed with the standard generally accepted methods: lipids, aminotransferases, gamma‑glutamyl transpeptidase (GGTP), glucose, glycosylated hemoglobin, insulin, HOMA index, glomerular filtration rate (GFR) were determined according to the CKD‑EPI formula. Blood Levels of cytokeratin‑18, adiponectin, fetuin A, tumor necrosis factor‑α, and interleukin‑6 were determined by ELISA. The indicators of malondialdehyde and diene conjugates and superoxide dismutase were determined by spectrophotometry. Patients were divided into two groups. Group A patients (n=23) received losartan 25—50 mg/day in combination with indapamide 1.5—2.5 mg and atorvastatin 10—20 mg/day for 12 months. Group B patients (n=22) received extended complex treatment (ECT) losartan 25—50 mg/day in combination with indapamide 1.5—2.5 mg and atorvastatin 10—20 mg/day in combination with complex ω‑3 polyunsaturated fatty acids in a dose of 2 g/day and ursodeoxycholic acid (UDCA) in a dose of 10 mg/kg/day for 12 months.&#x0D; Results. Both regimens of 12‑month complex treatment of patients with NAFLD and RPAH effectively improved parameters of blood pressure, carbohydrate, lipid metabolism, renal function, inflammation and oxidative stress indicators. There was no significant difference in the effects on anthropometric indicators and systolic BP (p&gt;0.05). Meanwhile, there was a significant difference in favor of ECT according to the diastolic BP — the difference in the shift of the indicator was 2.213 mm Hg (p&lt;0.01). Almost all laboratory «liver» indicators, except for ALT, decreased to a greater extent in patients receiving the ECT regimen. Thus, according to the GGTP the shift difference was 13.970 U/L (p&lt;0.001), and according to the cytokeratin‑18 the shift difference was 58.126 U/L (p&lt;0.001). There was also a significantly greater effect of ECT on fibrosis, steatosis and inflammation of the liver according to FibroMax data. Thus, the difference between shifts was 0.08 (p&lt;0.01), 0.12 (p&lt;0.001) and 0.10 (p&lt;0.01), respectively. The results of the comparative assessment of lipid and carbohydrate metabolism indicators were heterogeneous. Thus, the shift in total cholesterol was significantly greater in the ECT group and was 0.621 mmol/L (p&lt;0.01). At the same time, the shift of the triglycerides was greater (–0.94±0.92 mmol/L) in this group, but had no significant difference with the shift of the group A –0.63±0.42 (p&gt;0.05). There was also a significant difference between shifts in glycosylated hemoglobin in favor of the ECT scheme, the difference was 0.197% (p&lt;0.05). According to other indicators of lipid and carbohydrate metabolism, there was a tendency towards the predominance of the ECT scheme, but no significant difference in shifts was found (p&gt;0.05). The difference in blood creatinine and GFR shifts was significant and was 6.806 mol/L and 6.156 ml/min/1.73 m2, respectively (p&lt;0.001). At the same time, the dynamics of the microalbuminuria in the two comparison groups were similar (p&gt;0.05).&#x0D; Conclusions. The treatment scheme of a 12‑month complex treatment with the addition of ω‑3 polyunsaturated fatty acids 2 g/day and UDCA 10 mg/kg/day is more effective in terms of impact on clinical and laboratory indicators.&#x0D;

Fluid Mechanics Approach to Perfusion Quantification: Vasculature Computational Fluid Dynamics Simulation, Quantitative Transport Mapping (QTM) Analysis of Dynamics Contrast Enhanced MRI, and Application in Nonalcoholic Fatty Liver Disease Classification.

We quantify liver perfusion using quantitative transport mapping (QTM) method that is free of arterial input function (AIF). QTM method is validated in a vasculature computational fluid dynamics (CFD) simulation and is applied for processing dynamic contrast enhanced (DCE) MRI images in differentiating liver with nonalcoholic fatty liver disease (NAFLD) from healthy controls using pathology reference in a preclinical rabbit model. QTM method was validated on a liver perfusion simulation based on fluid dynamics using a rat liver vasculature model and the mass transport equation. In the NAFLD grading task, DCE MRI images of 7 adult rabbits with methionine choline-deficient diet-induced nonalcoholic steatohepatitis (NASH), 8 adult rabbits with simple steatosis (SS) were acquired and processed using QTM method and dual-input two compartment Kety's method respectively. Statistical analysis was performed on six perfusion parameters: velocity magnitude | u | derived from QTM, liver arterial blood flow LBFa, liver venous blood flow LBFv, permeability Ktrans, blood volume Vp and extravascular space volume Ve averaged in liver ROI. In the simulation, QTM method successfully reconstructed blood flow, reduced error by 48% compared to Kety's method. In the preclinical study, only QTM |u| showed significant difference between high grade NAFLD group and low grade NAFLD group. QTM postprocesses DCE-MRI automatically through deconvolution in space and time to solve the inverse problem of the transport equation. Comparing with Kety's method, QTM method showed higher accuracy and better differentiation in NAFLD classification task. We propose to apply QTM method in liver DCE MRI perfusion quantification.

A STUDY OF NON ALCOHOLIC FATTY LIVER DISEASE PATIENTS WITH METABOLIC SYNDROME

Background: Non-alcoholic fatty liver disease (NAFLD) has been rising in incidence in the past two decades in developing nations like India as well as in many western nations and is being taking over the position of most common liver disease in the world. To study ultrasonographically diagnosed NAFLD with va Aims &amp; objectives: rious grades and its association with metabolic syndrome and its components. The study was cross sectional descri Material and Methods: ptive study of patients with NAFLD, attending OPD and in patients of the Department of general Medicine, tertiary care hospital. All patients with as NAFLD were investigated for metabolic syndrome according to the NCEP ATP 3 Criteria and association between NAFLD and metabolic syndrome was studied. Results: There was a signicance association between fasting blood sugar level and USG grading of NAFLD. Age, HDL, VLDL &amp; SBP were close to the statistical signicant level . NAFLD found to be in higher degree in all Conclusions: the components of metabolic syndrome. Its early screening will help in modifying the disease course, delaying complications and will also play a major role in preventive complication.

Correlation between Serum Uric Acid and Non-Alcoholic Fatty Liver Disease: A Cross-Sectional Study

Background: Non-alcoholic fatty liver disease (NAFLD) is one of the important health issues with high prevalence worldwide. However, there is no approved medication for that. As one of the indicators of metabolic syndrome, uric acid might play a role in the pathogenesis of NAFLD. In this study, we aimed to determine the correlation between serum uric acid level, liver enzymes, and ultrasonographic grading of NAFLD.&#x0D; Methods: This cross-sectional study included patients aged 18-65 with NAFLD. Patients with other metabolic disorders and a history of using alcohol or medications that alter uric acid levels were excluded. The patients' serum uric acid, alanine aminotransferase (ALT), aspartate aminotransferase (AST) levels, and ultrasonographic grading of NAFLD at baseline, third month, and sixth month were collected.&#x0D; Results: Of the 3000 patients, 500 patients met the eligibility criteria. The results showed that there is a significant positive relationship between ALT and serum uric acid level at the first (P= 0.01), third (P=0.01), and sixth month (P=0.01). Furthermore, there was a significant positive correlation between AST and serum uric acid level at the sixth month (P= 0.001). The comparison of 249 patients' ultrasonographic grading showed no significant correlation with serum uric acid levels.&#x0D; Conclusion: To conclude, the serum uric acid level significantly correlates with ALT and AST over six months but not with the ultrasonographic grading. Further studies are required to determine the role of uric acid-lowering agents in the treatment of NAFLD.

A liver secretome gene signature-based approach for determining circulating biomarkers of NAFLD severity.

Non-invasive biomarkers of non-alcoholic fatty liver disease (NAFLD) supporting diagnosis and monitoring disease progression are urgently needed. The present study aimed to establish a bioinformatics pipeline capable of defining and validating NAFLD biomarker candidates based on paired hepatic global gene expression and plasma bioanalysis from individuals representing different stages of histologically confirmed NAFLD (no/mild, moderate, more advanced NAFLD). Liver secretome gene signatures were generated in a patient cohort of 26 severely obese individuals with the majority having no or mild fibrosis. To this end, global gene expression changes were compared between individuals with no/mild NAFLD and moderate/advanced NAFLD with subsequent filtering for candidate gene products with liver-selective expression and secretion. Four candidate genes, including LPA (lipoprotein A), IGFBP-1 (insulin-like growth factor-binding protein 1), SERPINF2 (serpin family F member 2) and MAT1A (methionine adenosyltransferase 1A), were differentially expressed in moderate/advanced NAFLD, which was confirmed in three independent RNA sequencing datasets from large, publicly available NAFLD studies. The corresponding gene products were quantified in plasma samples but could not discriminate among different grades of NAFLD based on NAFLD activity score. Conclusion: We demonstrate a novel approach based on the liver transcriptome allowing for identification of secreted hepatic gene products as potential circulating diagnostic biomarkers of NAFLD. Using this approach in larger NAFLD patient cohorts may yield potential circulating biomarkers for NAFLD severity.

Lifestyle Intervention for Patients with Nonalcoholic Fatty Liver Disease: A Randomized Clinical Trial Based on the Theory of Planned Behavior.

Introduction Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, accounting for about 25% and 33% of the world's adult population and Iranians, respectively. There is currently no effective therapeutic agent available for the treatment of NAFLD. However, lifestyle modifications aimed at weight loss have been introduced as a cornerstone of NAFLD management. The aim of the present study was to evaluate the effect of educational intervention on lifestyle and anthropometric indices in patients with NAFLD. Methods The randomized controlled clinical trial was performed on 87 overweight or obese patients with NAFLD, including intervention (n = 42) and control (n = 45) groups. The intervention received 8 training sessions based on theory of planned behavior (TPB), while the control groups received nutritional and physical activity recommendations from their internal specialist and nutritionist. Analyses were carried out based on data collected from TPB constructs and anthropometric indices (weight, body mass index (BMI), waist size, and waist-hip ratio (WHR)) at three stages (before intervention and two and 12 weeks after the intervention), as well as data obtained from liver enzymes (alanine aminotransferase (ALT) and aspartate aminotransferase (AST)), and ultrasound-based grading of NAFLD at two stages (before and 12 weeks after the intervention). Results After the intervention, a significant difference was found between the intervention and control groups, resulting in the increased mean scores of TPB constructs, decreased liver enzymes, and decreased degree of NAFLD ultrasound. In addition, the intervention group experienced more activity and healthy diet as compared with the control group. Anthropometric indices showed only a significant decrease in BMI in the intervention group (p < 0.05). Conclusions TPB-based training, as compared with traditional training, is a more effective and cost-effective strategy for altering nutritional behavior and physical activity of patients with NAFLD.

Efficacy and safety of dietary polyphenol supplementation in the treatment of non-alcoholic fatty liver disease: A systematic review and meta-analysis.

BackgroundDietary polyphenol treatment of non-alcoholic fatty liver disease (NAFLD) is a novel direction, and the existing clinical studies have little effective evidence for its therapeutic effect, and some studies have inconsistent results. The effectiveness of dietary polyphenols in the treatment of NAFLD is still controversial. The aim of this study was to evaluate the therapeutic efficacy of oral dietary polyphenols in patients with NAFLD.MethodsThe literature (both Chinese and English) published before 30 April 2022 in PubMed, Cochrane, Medline, CNKI, and other databases on the treatment of NAFLD with dietary polyphenols was searched. Manual screening, quality assessment, and data extraction of search results were conducted strictly according to the inclusion and exclusion criteria. RevMan 5.3 software was used to perform the meta-analysis.ResultsThe RCTs included in this study involved dietary supplementation with eight polyphenols (curcumin, resveratrol, naringenin, anthocyanin, hesperidin, catechin, silymarin, and genistein) and 2,173 participants. This systematic review and meta-analysis found that 1) curcumin may decrease body mass index (BMI), Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Triglycerides (TG) total cholesterol (TC), and Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) compared to placebo; and curcumin does not increase the occurrence of adverse events. 2) Although the meta-analysis results of all randomized controlled trials (RCTs) did not reveal significant positive changes, individual RCTs showed meaningful results. 3) Naringenin significantly decreased the percentage of NAFLD grade, TG, TC, and low-density lipoprotein cholesterol (LDL-C) and increased high-density lipoprotein cholesterol (HDL-C) but had no significant effect on AST and ALT, and it is a safe supplementation. 4) Only one team presents a protocol about anthocyanin (from Cornus mas L. fruit extract) in the treatment of NAFLD. 5) Hesperidin may decrease BMI, AST, ALT, TG, TC, HOMA-IR, and so on. 6) Catechin may decrease BMI, HOMA-IR, and TG level, and it was well tolerated by the patients. 7) Silymarin was effective in improving ALT and AST and reducing hepatic fat accumulation and liver stiffness in NAFLD patients.ConclusionBased on current evidence, curcumin can reduce BMI, TG, TC, liver enzymes, and insulin resistance; catechin can reduce BMI, insulin resistance, and TG effectively; silymarin can reduce liver enzymes. For resveratrol, naringenin, anthocyanin, hesperidin, and catechin, more RCTs are needed to further evaluate their efficacy and safety.